The term cancer commonly refers to a broad group of diseases characterized by unregulated cell growth that forms malignant tumors. Cancer therapies generally kill cells, ideally primarily tumor cells but also normal cells. Current methods for determining the effectiveness of cancer therapy include invasive procedures such as biopsies, as well as imaging methods such as CT scan, magnetic resonance imaging (MRI) scan, and positron emissions tomography (PET) scan. However, to take advantage of such non-invasive methods, the tumors typically must reduce in size enough that the imaging procedures can detect a difference. To aid in determining whether a new anti-cancer drug or anti-tumor drug has efficacy in killing cancer or tumor cells, or whether an anti-cancer drug or anti-tumor drug has efficacy against a particular tumor or cancer, it would be very useful to have a method to determine non-invasively the amount of tumor or cancer cell killing in a patient relative to normal cell killing. Methods and compositions for non-invasive determination of circulating biomolecules following tumor or cancer cell killing by a therapeutic or putative therapeutic are also desirable.
MicroRNAs are small (approximately 22 nucleotide) single-stranded RNAs found predominantly in the cytoplasm of higher eukaryotes (plants and multi-cellular animals). Their primary function is to regulate gene expression by binding to specific target mRNAs, usually in the 3′-untranscribed region (3′-UTR), and inhibiting their translation while promoting their destruction. There are over 1,000 identified miRNAs in mouse and over 2,000 in humans. Most miRNAs are thought to have multiple mRNA targets that could number in the hundreds. Many mRNAs that are regulated by miRNAs have binding sites in their 3′-UTRs for multiple miRNAs. Some miRNAs are fairly ubiquitously expressed; others exhibit highly restricted tissue-specific expression.
Recent research has discovered that a subset of a few hundred miRNAs is present and readily detectable in the serum and plasma of mammals. The profile of the serum/plasma miRNAs is remarkably stable in normal healthy animals, but can vary in disease states or in response to drugs or chemically induced toxicities. The serum/plasma miRNA profile differs from that for the cellular component of the blood.
A growing literature is beginning to reveal many examples of serum/plasma miRNA profiles that provide biomarkers for diagnosis and prognosis in diseases such as liver fibrosis, myocardial malfunction, and various cancers. Serum/plasma miRNA profiling has also been shown to predict drug efficacy, toxicity, and specific organ and tissue damage.